Methods for the amelioration of episodes of acute or chronic ulcerative colitis

• US 7,928,132 B2
• Filed: 08/06/2004
• Issued: 04/19/2011
• Est. Priority Date: 08/06/2004
• Status: Expired due to Fees

• Current Assignee: Douglas J. Goetz, Ohio University
• Original Assignee: Ohio University
• Inventors: Kohn, Leonard D., Lewis, Christopher J., Gonzalez-Murguiondo, Mariana, Dagia, Nilesh D., Napolitano, Giorgio, Harii, Norikazu, Benavides-Peralta, Uruguaysito, Goetz, Douglas J.
• Primary Examiner(s): Spivack; Phyllis G.
• Application Number:
  US10/912,948
• Publication Number:
  US 20060058365A1
• Time in Patent Office: 2,447 Days
• Field of Search: None
• US Class Current: 514/386
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods of ameliorating episodes of accute or chronic colitis are provided by using methimazole derivatives and tautomeric cyclic thiones in combination with another pharmaceutical compound.

Claims

1. A method for the amelioration of episodes of acute or chronic ulcerative colitis in a mammal comprising administering to the mammal a pharmaceutical composition comprising an active compound having the formula selected from the group consisting of:

2. The method of claim 1, wherein each substituted C₁-C₄ alkyl is a C₁-C₄ alkyl group substituted with groups selected from one or more of hydroxyl groups, alkyoxyl groups, and halogens.

3. The method according to claim 2, wherein the active compound is administered in conjunction with one or more drugs, agents or therapeutics selected from the group consisting of:

glucocorticoids, 5-lipoxygenase inhibitors, β

-2 adrenoceptor agonists, muscarinic M1 and M3 antagonists, muscarinic M2 agonists, NK3 antagonists, LTB4 antagonists, cysteinyl leukotriene antagonists, bronchodilators, PDE4 inhibitors, PDE inhibitors, elastase inhibitors, MMP inhibitors, phospholipase A2 inhibitors, phospholipase D inhibitors, histamine H1 antagonists, histamine H-3 antagonists, dopamine agonists, adenosine A2 agonists, NK1 and NK2 antagonists, GABA-b agonists, nociceptin agonists, expectorants, mucolytic agents, decongestants, antioxidants, anti-IL-8 anti-bodies, anti-IL-5 antibodies, anti-IgE antibodies, anti-TNF antibodies, IL-10, adhesion molecule inhibitors, and growth hormones.

4. The method according to claim 2, wherein the pharmaceutical composition comprises from about 0.01% to about 25% of the active compound and from about 75% to about 99.99% of a pharmaceutically-acceptable carrier.

5. The method according to claim 1, wherein the active compound has the formula

6. The method according to claim 1, wherein the active compound has the formula:

7. The method according to claim 1, wherein the active compound has the formula:

8. The method according to claim 1, wherein the active compound has the formula:

9. The method according to claim 1, wherein Z is SR³ and one of the Y groups is the phenyl moiety.

10. The method according to claim 1, wherein R¹ and R⁴ are H.

11. The method according to claim 1, wherein Z is SR³ and R³ is a methyl, and one of the Y groups is the phenyl moiety wherein R¹ and R⁴ are H, and the R² group is methyl.

12. The method according to claim 1, wherein one of the Y groups is the phenyl moiety, wherein R¹ and R⁴ are H, and both R² groups are methyl.

13. The method according to claim 1, wherein the active compound is:

14. The method according to claim 1, wherein the active compound is:

15. The method according to claim 1, wherein the active compound is:

16. A method for the amelioration of episodes of acute or chronic ulcerative colitis in a mammal comprising administering to the mammal a pharmaceutical composition comprising an active compound having the formula selected from the group consisting of:

17. A method for the amelioration of episodes of acute or chronic ulcerative colitis in a mammal comprising administering to the mammal a pharmaceutical composition comprising an active compound having the formula selected from the group consisting of: